Escitalopram, a selective serotonin re-uptake inhibitor, is a well known drug which has been on the market for the treatment of disorders relating to mood as well as anxiety. The structure of escitalopram is provided immediately below.

Citalopram is the racemate corresponding to escitalopram and was first disclosed in U.S. Pat. No. 4,136,193. Escitalopram was first disclosed in EP 0 347 066 and is currently marketed as an oxalate salt Since the publication of the above identified patents, a number of processes for the preparation and purification of escitalopram or pharmaceutically acceptable salts thereof have been devised.
One such preparation, as represented in scheme 1, involves starting with cyanophthalide. The Grignard condensation of 5-cyanophthalide with 4-fluorophenylmagnesium bromide gives 1-(4-fluorophenyl)-1-hydroxy-1, 3-dihydroisobenzofuran-5-carbonitrile bromo magnesium salt (II), which equilibrates to the benzophenone (III). A new Grignard condensation of (III) with 3-(dimethylamino)propylmagnesium chloride affords the bis(magnesium) salt, which is hydrolyzed with acetic acid to provide the diol (IV) as a racemic mixture (See U.S. Pat. No. 4,650,884 for details). The optical resolution of the racemic diol (IV) can be performed by HPLC via chiral labile ester derivatives or a resolution process using (+)-di-p-toluoyltartaric acid. The resulting (S)-diol (V) is cyclized by reaction with methanesulfonyl chloride to afford escitalopram. The free base can be converted to a pharmaceutically acceptable salt such as the oxalate.

Unfortunately, and as is well-known in those skilled in the art impurities are inevitably formed during Grinard reactions and these impurities are difficult to separate from the desired end product. At times, extensive and time consuming purification procedures such as HPLC techniques are required to obtain purified escitalopram. Even by using a recrystallization procedure, the impurities remain in an undesired amount.
Where the production of escitalopram manufacture involves a procedure substantially similar to that described in scheme 1, the impurities as shown in the compounds of formulas VI-IX are:

Thus, there still remains the need to devise efficient and more economical purification procedures especially for use on an industrial scale where, for example, the use of HPLC may be prohibitively expensive and time consuming.
The inventors have now discovered an alternative process of purifying escitalopram by reducing the amount of the above mentioned impurities substantially without using potentially time consuming crystallization techniques or expensive HPLC techniques. Rather the inventors have found that by the careful selection of solvents and the careful manipulation of the pH, escitalopram may be isolated in very high purity while removing the impurity of formula VI as well as the impurity of formula VII in a desired amount.